Ethyl alcohol (ethanol) is probably the most widely-abused drug in modern society. Changes in glucose homeostasis related to alcoholism constitute important and occasionally grave clinical problems. Several studies have established the hypoglycemic potential of ethanol in humans and in experimental animals after prolonged starvation. However, we have shown that simultaneous administration of ethanol and glucose, induced glucose intolerance and inhibition of insulin release in young adult male rats. Ethanol inhibits glucose mediated insulin release from isolated islets of young adult male rats. Glucagon release, from isolated islets of young adult rats, in response to low glucose concentration is significantly higher tin the presence of ethanol. The process of aging is associate with a progressive decrease in carbohydrate tolerance and glucose induced insulin secretion. I have observed that older male rats have a significantly higher basal (fasting) plasma glucagon levels compared with those in young adult male rats. These studies suggest that both ethanol and the aging process individually exhibit diabetogenic effects on the release of both pancreatic glucoregulatory hormones like insulin and glucagon, as well as on peripheral glucose utilization. However, to my knowledge, there is no study correlating the effects of ethanol and aging together on glucose homeostasis. Therefore, it is important to study, in detail the mode of the influence of chronic ethanol intake on carbohydrate metabolism in aged animals. In general, studies on rats confirm the data derived from human experimentation. Therefore, the proposed research is to determine the effects of chronic ethanol ingestion on glucose homeostasis in rats (4, 15 and 24 months old). Ethanol (liquid diet) will be offered to 2, 13 and 22 month old rats for two months. Glucose tolerance tests, insulin sensitivity tests (in vivo and in vitro), and both insulin and glucagon release from isolated islets of these rats will be studied. To delineate whether the ethanol effects are reversible or not, ethanol liquid diet fed rats will be fed control liquid diet for up to one month after two months of chronic ethanol ingestion. Glucose tolerance tests, insulin sensitivity tests (in vivo & in vitro) as well as both insulin and glucagon release from isolated islets of these rats will be performed.